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Allergy Recapitulates Phylogeny

The views expressed are those of the author and are not necessarily those of Scientific American.


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For many years I lived in fear of my allergies. While I never had any life-threatening reactions, I developed new allergies with alarming frequency throughout my childhood. First, hives from petting my 4th grade best friend’s bunny, then the standard seasonal allergies of temperate forest springtime, then an increasingly long list of raw fruits, vegetables, and nuts that made my mouth and throat itchy and swollen. I began to think that soon I would be allergic to everything.

A trip to the allergist hoping for some sort of magic or at least a prescription of Zyrtec gave me something better: a diagnosis. I have Oral Allergy Syndrome, a cluster of localized allergies to fresh fruits and vegetables that is pretty common in people with seasonal allergies.

Allergy is your body overreacting to harmless things. The immune system’s antibodies recognize a normally inoffensive protein and activate the immune system to fight it off, causing all of the symptoms you know and hate. For a lot of seasonal allergy sufferers like me, building up antibodies against pollen proteins also means reacting to when that protein shows up in other plants, including fruits and vegetables. Some antibodies bind to the sequence of amino acids in the protein, but many bind to the 3D shape of the protein. Cooking brings the temperature high enough to denature the 3D structure, preventing the antibody from binding and making it edible again.

I’m allergic to birch trees, whose major allergen is called Bet v 1 (Allergen proteins are named based on the Latin name of their host. Birch trees are Betula verrucosa, hence Bet v 1). Bet v 1 is a protein that helps the plant respond to pathogens and shows up in lots of other fruits and vegetables, making me allergic to things like (in rough order of allergenicity): peaches, cherries, almonds, plums, apricots, apples, pears, berries, kiwis, soy, carrots, celery, tomatoes, peppers, parsley, and potatoes.

As the list got longer I assumed I was allergic to something unless proven otherwise. Preferring to err on the side of caution I avoided all uncooked fruits and salads. But more recently, as I started to learn more about plants (woefully lacking from typical molecular biology education) I started to learn the connections between things I was allergic to and things that I could eat. Cucumbers are in the same family as melons! Cherries and almonds are closely related! Broccoli and cabbage are the same species! My allergies started to seem less random, and it became easier to talk with waiters and friends throwing dinner parties about what to avoid.

Mapping fruits and vegetables I can and can’t eat onto the evolutionary tree for flowering plants made the connections even clearer. In the diagram below, modified from a tree constructed by the Angiosperm Phylogeny Group, plant families highlighted in red contain things I’m allergic to, ones in green I can eat, and ones left black are unknown or inedible:

There is a pretty clear split between monocots and eudicots, and the allergenic plants definitely cluster in the rosids and asterales, close to the order Fagales that includes the dreaded birch tree. The clustering makes sense, as proteins should be more closely related in more closely related species, although I’m not really sure how the Cucurbitales, including the non-allergenic cucumbers and melons, can be so close to the mother allergen. It’s also still an open question why only the birch version of this protein that is part of a ubiquitous superfamily present across many different organisms causes this kind of allergic response.

One notable finding from this mapping exercise is that the strength of my allergic reaction seems to correlate with the plant’s position on the phylogenetic tree. From throat-closing peaches and cherries down to mildly irritating (yet delicious) cilantro my allergic reactions do a pretty good job of aligning to phylogenetic relationships. More evolutionary distant versions of Bet v 1 share less and less similarity with the original allergen, so my antibodies bind less well, causing a weaker allergic reaction.

These phylogenetic trees are usually made by comparing the similarity of gene sequences that are shared between all of the members, often a part of the ribosomal RNA. Rebuilding the tree based on Bet v 1 with software that aligns protein sequences:


and clusters them based on relatedness:

yields a very similar tree! These phylogenetic trees now make it easier for me to know if I’m allergic to something and how strong my reaction would be by simply looking up taxonomic information on wikipedia rather than tasting. I still can’t eat any of these things (although my iGEM students did try to engineer non-allergenic plants for me), but thanks to science I’m at least not afraid of my allergies anymore.

Christina Agapakis About the Author: Christina Agapakis is a biological designer who blogs about biology, engineering, engineering biology, and biologically inspired engineering. Follow on Twitter @thisischristina.

The views expressed are those of the author and are not necessarily those of Scientific American.



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  1. 1. blackbetty 9:12 pm 09/18/2011

    Thank you so much for this post. I also suffer from OAS and seasonal allergies and react most strongly to plants in the birch family.

    Link to this
  2. 2. JamesDavis 8:24 am 09/19/2011

    A person can tell when their immune system is out of whack and your immune system has been out of whack your whole life. If it is possible, at this late date in your life, for you to stabilize your immune system then your allergies may go away. For about six months, why don’t you stop taking your allergy medications, if you are taking over the counter allergy medications, and replace them with 500 mg of echinacea/goldenseal and 11,000 units of bee pollen/bee propolis. You already know what you can and cannot eat so there should be no danger stopping your allergy medication for that short period of time. Since you have a really good understanding of plants and trees, you know that these are safe and has no side effects. For this long time you have had allergies, it may take about six to eight months to re-stabilize your immune system and your allergies should disappear.

    I have a masters in herbal medicine and I have worked with a lot of children with seasonal allergies, including pet allergies and these four simple products works wonders for them…but in a much smaller dosage.

    Link to this
  3. 3. Stephen@DropYourAllergies 10:36 am 09/19/2011

    Christina:
    This is the Best Oral Allergy Syndrome overview that I have seen / read.

    While my training is Business, for the last 8 yr our MD Medical director & I have been supporting USA Docs with IgE Enviro allergy Blood Testing,following by Custom formulated Immuno-Allergy / Sublingual DROPs. May I suggest you look into for your Enviro Allergies.

    As a BTW, together with my Vet Dermatologist Medical Director we have launched a Immuno Sublingual Product called Doggy GOO which Sublingually builds Immune Tolerance to enviro Allergies in our Itchy Canine population.

    Link to this
  4. 4. vesperlight 10:56 am 09/19/2011

    This is a great explanation of this problem. When my son was little, nobody every believed that he was allergic to carrots, etc. Who is? Fortunately, the proteins that he reacts to break down with cooking enough that he can eat cooked vegetables (though he still doesn’t like the much.)

    One possible long term solution might be the GAPS diet, a two year process which works by healing the gut, restoring a large portion of the body’s immune system and making it healthy again.

    Link to this
  5. 5. kclancy 11:43 am 09/19/2011

    We are kindred spirits in more ways than I realized! I have this as well — major seasonal allergies, can’t eat apples, pears, peaches, nectarines, cherries, or snap peas raw. I’ve been taking allergy shots for about a year now, and there is a chance that reducing my primary allergies (birch and lots of other stuff) will reduce or remove my allergies to these fruits. I tried a bite of a pear last week and it had no effect on me, but I’m not trying it out much more than that until I am farther along with my shots.

    I find the raw fruit allergies particularly devastating, and it makes planning snacks so hard… particularly because I am also gluten intolerant. Do you know if the protein we have a reaction to is found in higher quantities in different parts of the fruit? In addition to cooking, I have had some success reducing my reaction by peeling fruit.

    But I still keep an Epi Pen on me at all times.

    Link to this
  6. 6. jgrosay 4:23 pm 09/19/2011

    What a good information on the phylogeny of allergens !. It’s very useful for the people involved in allergic persons care. By the way: some say the increase in allergy cases may be connected to a too early introduction of cereals in baby’s meals. Perhaps waiting until the child has one year of age or more would be wise. – Unproven statement -

    Link to this
  7. 7. sxdsteven 1:55 am 10/2/2011

    Of course, this article clearly clarifies how the allergy comes from, and how many kinds of allergy there are, how different allergy related to each others, and using the theories from the biochemistory about genes to demonstrate different RNA sequence can show us that when different species’ RNA sequence become similar, they are more close in relatedness.

    Also, the author use a simple but quite useful way to help readers to understand this complex scientific essay, that is mapping. Which help people to know these concept by relating each elements, readers don’t need to find the keyword in lines and certainly makes less confusion.

    Link to this
  8. 8. sxdsteven 1:55 am 10/2/2011

    Of course, this article clearly clarifies how the allergy comes from, and how many kinds of allergy there are, how different allergy related to each others, and using the theories from the biochemistory about genes to demonstrate different RNA sequence can show us that when different species’ RNA sequence become similar, they are more close in relatedness.

    Also, the author use a simple but quite useful way to help readers to understand this complex scientific essay, that is mapping. Which help people to know these concept by relating each elements, readers don’t need to find the keyword in lines and certainly makes less confusion

    Xiaodong Sun

    Link to this
  9. 9. allergyspecific 3:39 pm 10/2/2011

    There are a few good studies on specific immunotherapy and oral allergy syndrome. In an observational study by Karl-Christian Bergmann, MD, et al, Patients that had pollen-induced rhinoconjunctivitis
    and Oral Allergy Syndrome responded favorably to birch specific sublingual immunotherapy and showed ‘very much improvement’ in their oral allergy syndrome after 12 months. Treat the birch allergy, and the oral allergy decreases.

    Link to this
  10. 10. annemarsh12 11:13 pm 10/2/2011

    I am only allergic to one thing, so it’s hard for me to grasp the concept of being afraid of what I eat. But, it’s interesting to me that Christina figured out a way to change that. It’s also interesting that allergies can be grouped together based on their proteins to make them easier to avoid. I never thought of it that way, and I think that it should be more widely known. If more people with food allergies knew how to trace the origin of their allergies, I believe that less people with food allergies would be scared of it.

    Link to this
  11. 11. Paleojo 8:24 pm 10/10/2011

    I enjoyed the article as well as the discussion on blogging heads with Maggie.

    I seem to have the oral allergy syndrome. Fortunately I am affected by only two foods. One is hazelnuts and interestingly the other is dungeness crab. Hazelnuts are native to my region and are in the same family as birch. But crab? What if any relationship might dungeness crab have with hazelnuts? Is this evidence that the very ancient common ancestor of dungeness crab and hazelnuts had this protein?

    Link to this

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